Page 109 - Color_Atlas_of_Physiology_5th_Ed._-_A._Despopoulos_2003

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the resulting inflammation (! A2, 4) also damages blasts, while IFN-γ is liberated from activated T cells
cells involved in nonspecific defense and, in some and NK cells. Virus-infected cells release large quanti-
cases, even other endogenous cells. ties of IFNs, resulting in heightened viral resistance in
non-virus-infected cells. Defensins are cytotoxic
Opsonization (! A1, 2) involves the binding of peptides released by phagocytes. They can exert un-
opsonins, e.g., IgG or complement factor C3b, to specific cytotoxic effects on pathogens resistant to
specific domains of an antigen, thereby en- NK cells (e.g., by forming ion channels in the target
hancing phagocytosis. It is the only way to cell membrane).
make bacteria with a polysaccharide capsule Macrophages arise from monocytes that mi-
phagocytable. The phagocytes have receptors grate into the tissues. Some macrophages are
on their surface for the (antigen-independent) freely mobile (free macrophages), whereas
Fc segment of IgG as well as for C3b. Thus, the others (fixed macrophages) remain restricted
antigen-bound IgG and C3b bind to their re- to a certain area, such as the hepatic sinus
spective receptors, thereby linking the rather (Kupffer cells), the pulmonary alveoli, the in-
unspecific process of phagocytosis with the testinal serosa, the splenic sinus, the lymph
specific immune defense system. Carbohy- nodes, the skin (Langerhans cells), the synovia
drate-binding proteins (lectins) of plasma, (synovial A cells), the brain (microglia), or the
called collectins (e.g. mannose-binding pro- endothelium (e.g., in the renal glomeruli). The
tein), which dock onto microbial cell walls, also mononuclear phagocytic system (MPS) is the
acts as unspecific opsonins. collective term for the circulating monocytes
The complement cascade is activated by an-
Blood tigens opsonized by Ig (classical pathway) as in the blood and macrophages in the tissues.
Macrophages recognize relatively unspecific
4 well as by non-opsonophilic antigens (alterna- carbohydrate components on the surface of
tive pathway) (! A1). Complement com- bacteria and ingest them by phagocytosis. The
ponents C3a, C4a and C5a activate basophils macrophages have to be activated if the patho-
and eosinophils (! A4). Complement com- gens survive within the phagosomes (! below
ponents C5 –C9 generate the membrane-attack and B3).
complex (MAC), which perforates and kills
(Gram-negative) bacteria by cytolysis (! A3). Specific Immunity: Cell-Mediated Immune
This form of defense is assisted by lysozyme Responses
(= muramidase), an enzyme that breaks down Since specific cell-mediated immune re-
murein-containing bacterial cell walls. It oc- sponses through “armed” T effector cells need
curs in granulocytes, plasma, lymph, and a few days to become effective, this is called
secretions. delayed-type immune response. It requires the
Natural killer (NK) cells are large, granular participation of professional antigen-pres-
lymphocytes specialized in nonspecific enting cells (APCs): dendritic cells, macro-
defense against viruses, mycobacteria, tumor phages and B cells. APCs process and present
cells etc. They recognize infected cells and antigenic peptides to the T cells in association
tumor cells on “foreign surfaces” and dock via with MHC-I or MHC-II proteins, thereby
their Fc receptors on IgG-opsonized surface delivering the co-stimulatory signal required
antigens (antibody-dependent cell-mediated for activation of naive T cells. (The gene loci for
cytotoxicity, ADCC; ! A3). Perforins exocytosed these proteins are the class I (MHC-I) and class
by NK cells form pores in target cell walls, II (MHC-II) major histocompatibility com-
thereby allowing their subsequent lysis (cy- plexes (MHC)), HLA (human leukocyte antigen)
tolysis). This not only makes the virus unable to is the term for MHC proteins in humans. Virus-
proliferate (enzyme apparatus of the cell), but infected dendritic cells, which are mainly lo-
also makes it (and other intracellular patho- cated in lymphatic tissue, most commonly
gens) subject to attack from other defense serve as APCs. Such HLA-restricted antigen
mechanisms. presentation (! B1) involves the insertion of
Various interferons (IFNs) stimulate NK cell activity: an antigen in the binding pocket of an HLA pro-
96 IFN-α, IFN-" and, to a lesser degree, IFN-γ. IFN-α and tein. An ICAM (intercellular adhesion mole-
IFN-" are released mainly from leukocytes and fibro- cule) on the surface of the APC then binds to
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Despopoulos, Color Atlas of Physiology © 2003 Thieme
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